MEDICAL VIROLOGY

LECTURE 1
General properties and Classification of
Viruses
• Term virus (Latin for
poisonous liquid)
• The existence of
viruses was first
suspected in the
nineteenth century
when it was shown
that filtered extract
of infective material
passed through
filters (filterable
material)
 VIRUSES
•Order (-virales)
•Family (-viridae)
•Subfamily (-virinae)
•Genus (-virus)
•Species Species names generally take
the form of [Disease] virus

Viruses are the smallest infectious agents

(20-300 nm in diameter), and contain only
one kind of nucleic acid (DNA or RNA)
encased in a protein shell which may be
surrounded by a lipid containing membrane.
They are obligate intracellular parasites.
• Are Viruses living or nonlivinig??
• There is an ongoing debate as to whether viruses
are living or nonliving; the view taken depends on
how life is defined.
• Viruses are therefore parasites of cells, and are
dependent on their hosts for most of their
requirements, including

➢ •building-blocks such as amino acids and

nucleosides;
➢ • protein-synthesizing machinery (ribosomes);
➢ • energy, in the form of adenosine triphosphate
 Definitions in virology
• Capsid: The
protein shell (or
coat) that
surrounds the
nucleic acid
genome.

• Capsomeres: The
morphological
units that form
the capsid and
represent clusters
of polypeptides.
Definitions in virology
• Nucleocapsid: The protein-
nucleic acid complex
representing the packaged
form of the viral genome.

• Virion: The complete virus

particle. In some instances
(e.g. picornaviruses) it is
identical to the nucleocapsid.
In more complex viruses
(e.g. herpesviruses) it
includes the nucleocapsid plus
the envelope.
 Definitions in virology
• Envelope: A lipoprotein
membrane that surrounds
some virus particles, it is
acquired during viral
maturation by budding
through the cellular
membrane. There are
frequently glycoprotein
spikes on the surface, that
play role in attachment of
virus to host cell.
Viral Structure - Overview

Nucleic acid
Nucleocapsid
Capsid

Envelope protein
Viral envelope**
Membrane protein
Spike protein

Schematic overview of the structure of animal viruses

** does not exist in all viruses
• Defective virus: A virus particle that is functionally deficient in some aspect of
replication.
• Envelope: A lipid-containing membrane that surrounds some virus particles. It is
acquired during viral maturation by a budding process through a cellular
membrane
• Virus-encoded glycoproteins are exposed on the surface of the envelope. These
projections are called peplomers.
• Nucleocapsid: The protein–nucleic acid complex representing the packaged form
of the viral genome. The term is commonly used in cases in which the
nucleocapsid is a substructure of a more complex virus particle.
• Structural units: The basic protein building blocks of the coat. They are usually
a collection of more than one nonidentical protein subunit. The structural unit is
often referred to as a protomer.
• Subunit: A single folded viral polypeptide chain. Virion: The complete virus
particle. In some instances (eg, papillomaviruses, picornaviruses), the virion is
identical
 Viral Symmetry
1-Icosahedral (cubic symmetry): the
capsomeres arranged in 20 triangles that
form a symmetric figure.

2-Helical: the capsomeres arranged in a

hallow coil that appears rod-shaped.

3-Complex: Neither cubic nor helical but

more complex.
Icosahedral symmetry
Helical symmetry
• Viruses have either an RNA or DNA genome (never both)
and are classified in families on the basis of their
genome (RNA or DNA) and whether it is single or double
stranded (SS or DS).

• Furthermore, Single-stranded RNA viruses are either a

negative (_RNA) or a positive (RNA) strand as this affects
their replication strategy.

• As a rule of thumb all DNA viruses, except those

belonging to Parvoviridae and Circoviridae are double
stranded, and all RNA viruses except those belonging to
Reoviridae and Birnaviridae are single stranded
 Classification of viruses
The two major components of the virus
used in the classification are:

1-The type of the nucleic acid (DNA

or RNA).

2-The capsid (its symmetry, size, and

whether it is enveloped or not).
Baltimore classification of viruses
 DNA Viruses
Envelope Capsid Medically important
Virus Family
presence symmetry viruses

Parvovirus No icosahedral B19 virus

Papovavirus No icosahedral Papillomavirus

Adenovirus No icosahedral Adenovirus

Hepadnavirus Yes icosahedral Hepatitis B virus

Herpesvirus Yes icosahedral HSV, VZV, CMV, EBV

Poxvirus Yes complex Smallpox, vaccinia viruses

 RNA Viruses
Envelope Capsid
Virus Familly Medically important viruses
presence symmetry
Picornavirus No Icosahedral Polio, rhino, hepatitis A virus
Calicivirus No Icosahedral Norwalk, hepatitis E virus
Reovirus No Icosahedral Reo, rota virus
Flavivirus Yes Icosahedral Yellow fever, hepatitisC virus
Togavirus Yes Icosahedral Rubella virus
Retrovirus Yes Icosahedral HIV, HTLV
Orthomyxovirus Yes Helical Influenza virus
Paramyxovirus Yes Helical Measles, Mumps, RSV
Rhabdovirus Yes Helical Rabies virus
Filovirus Yes Helical Ebola virus
Coronavirus Yes Helical Coronavirus
Arenavirus Yes Helical Lymphocytic choriomeningitis virus
Bunyavirus Yes Helical California encephalitis virus
Deltavirus Yes Uncertain Hepatitis D virus
RNA Viruses
Pathogenesis of Viral Diseases
Steps in viral pathogenesis
1. Entry and primary replication
2. Viral spread and cell tropism
3. Cell injury and clinical illness
4. Recovery from infection
5. Viral shedding
1- Entry and primary replication:
Most viruses enter the host through the
mucosa of the respiratory or GIT in which the
viruses replicate at these primary sites like
influenza (respiratory infection) or rotaviruses
(GIT infection); and produce the disease at
the portal of entry with no further systemic
spread.

Other viruses are introduced into the blood

stream by needles, blood transfusion (HBV,
HIV) or by insect vectors (arboviruses).
 Routs of viral entry
• Skin - Most viruses which infect via the skin require a breach in the
physical integrity of this effective barrier, e.g. cuts or abrasions.
Many viruses employ vectors, e.g. ticks, mosquitos or vampire bats
to breach the barrier.
• Conjunctiva and other mucous membranes - rather exposed site
and relatively unprotected
• Respiratory tract - In contrast to skin, the respiratory tract and all
other mucosal surfaces possess sophisticated immune defense
mechanisms, as well as non-specific inhibitory mechanisms
(cilliated epithelium, mucus secretion) which viruses must
overcome.
• Gastrointestinal tract - a hostile environment; gastric acid, bile
salts, etc. Viruses that spread by the GI tract must be adapted to this
hostile environment.
• Genitourinary tract - relatively less hostile than the above, but
less frequently exposed to extraneous viruses (?)
2- Viral spread and cell tropism:
A) Many viruses cause only a localized
infection as they are unable to spread.

B) Viruses that spread further from the

infecting site may use virus-encoded proteins
to direct their transport within the cell in a
way that enhances their spread via blood or
along nerves (polio and rabies viruses).
C) Other viruses, such as CMV, EBV and HIV, are
carried by infected blood cells to distant parts.

D) Measles virus, varicella-zoster virus and

rubella virus all spread via the respiratory
route but cause systemic infections. These
viruses have a transient ‘primary viraemia’ just
after infection to lodge in the RES (lymph
nodes and spleen). The virus replicates there
for a period of time (incubation period)
without causing disease symptoms. This is
followed by a second longer phase of viraemia
(secondary viraemia) when the infection is
spread to the target organs to manifest the
disease symptoms
 Cell Tropism
Viral affinity for specific body tissues (tropism) is
determined by
– Cell receptors for virus.
– Cell transcription factors that recognize viral
promoters and enhancer sequences.
– Ability of the cell to support virus replication.
– Physical barriers.
– Local temperature, pH, and oxygen tension enzymes
and non-specific factors in body secretions.
– Digestive enzymes and bile in the gastrointestinal
tract that may inactivate some viruses.
 3- Cell injury and clinical illness:
Destruction of virus-infected cells in the
target tissue and the physiologic
alterations produced in the host by the
tissue injury are partly responsible for
the development of disease.
 Cellular Pathogenesis
• Cells can respond to viral infections in 3 ways: (1) No apparent
change, (2) Death, and (3) Transformation
• Direct cell damage and death from viral infection may result
from
– diversion of the cell's energy
– Rupture of infected cell
– shutoff of cell macromolecular synthesis
– competition of viral mRNA for cellular ribosomes
– competition of viral promoters and transcriptional enhancers for cellular
transcriptional factors such as RNA polymerases, and inhibition of the
interferon defense mechanisms.
• Indirect cell damage can result from
– integration of the viral genome
– induction of mutations in the host genome
– inflammation
– host immune response.
Viruses might evoke autoimmunity
• Evoking an autoimmune response that affects
uninfected cells
– Mimicry
– Exposing protected sites
– Infecting immune cells - B cell antibody
production against variety of proteins
– Hyperexpression of MHC
 4- Recovery from infection:
The host either submits or recovers from
the viral infection. Recovery mechanisms
involve humeral, cell-mediated immunity,
interferon and other cytokines.

In acute infection recovery is associated

with viral clearance.
 5- Viral shedding
• The last stage in the pathogenesis is shedding
of the virus into the environment, shedding
usually occurs from body surfaces involved in
viral entry. It is the time at which the person
becomes infectious to the contacts. In some
viruses eg rabies human is a dead end and
virus shedding does not occur.
 Viral persistence
1. Chronic infection: in which the virus can be
continuously detected, often at low levels;
severe, mild clinical feature may be evident e.g.
HBV (unfinished battle).

1. Chronic carrier: The patient who has been

infected with certain virus continues to produce
significant amount of the virus for a long
period. e.g. HBV and HCV (Immune system
adapts to the presence of the virus with no
symptoms)
3. Latent infections: in which the virus persists in an
occult or cryptic form most of the time. There will
be intermittent flair-ups. HSV type 1 is latent in the
trigeminal ganglia (virus hides and hits).

4. Slow virus infections: Prolonged period between the

initial infection and the onset of the disease, which
is usually measured in years. Subacute sclerosing
panencephalitis (SSPE) which follows several years
after measles virus infection, and the second
disease is progressive multifocal
leukoencephalopathy (PML) caused by JC virus a
papovavirus (gradual change in host-microbe
reaction)
• Viruses are able to persist to cause chronic infection:

• (1) by escaping the immune system by constantly

mutating e.g. HIV;

• (2) by downregulating the host immune system e.g.

CMV, which codes for proteins that reduce the
expression of major histocompatibilitycomplex (MHC)
class 1 receptors on the cell surface;

• (3) by integrating in the host genome and replicating

with the cells e.g. HIV, hepatitis B virus (HBV).
Other slow infections in human are caused by
Prions: protein-containing particles with no
detectable nucleic acid that is highly resistant
to inactivation by heat, formalin, and UV light
that inactivate the viruses.
They cause CNS diseases like Kuru and
Creutzfeldt-Jakob diseases which are called
transmissible spongiform encephalopathies.
And also mad cow disease.
Clinical latency
 Infectiou Cell death Signs/ Duration of
s progeny symptoms infection
Acute + + + S <3 wks
Inapparent + + - S
Chronic + + +/- L
Persistent <<+ - - L
Latent - - - L
Slowly + + Eventually L
progressive +
Tumorigenic +/- - + L
 Outcome of Viral Infection
• Acute Infection
– Recovery with no residue effects
– Recovery with residue effects e.g. acute viral encephalitis
leading to neurological sequelae.
– Death
– Proceed to chronic infection
• Chronic Infection
– Silent subclinical infection for life e.g. CMV, EBV
– A long silent period before disease e.g. HIV, SSPE, PML
– Reactivation to cause acute disease e.g. herpes and shingles.
– Chronic disease with relapses and excerbations e.g. HBV, HCV.
– Cancers e.g. EBV, HTLV-1, HPV, HBV, HCV, HHV-8
Viral Replication
Stages of viral Growth cycle
1- Attachment and penetration
2- Uncoating of the viral genome
3- Early viral mRNA synthesis
4- Early viral protein synthesis
5- Viral genome replication
6- Late viral mRNA synthesis
7- Late viral protein synthesis
8- Progeny virion assembly
9- Virion release from the cell